Syk inhibition with fostamatinib leads to transitional B lymphocyte depletion

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• 作者：Paul M. Barr^a ; Chungwen Wei^b ; James Roger^b ; Julia Schaefer-Cutillo^a ; Jennifer L. Kelly^a ; Alexander F. Rosenberg^b ; John Jung^b ; Iñ ; aki Sanz^b ; ¹ ; ^{Ignacio_Sanz@URMC.Rochester.edu} ; Jonathan W. Friedberg^a ; ¹ ; ^{jonathan_friedberg@urmc.rochester.edu}
• 关键词：B-cell antigen receptor ; Signaling therapies ; Transitional B cells ; Fostamatinib
• 刊名：Clinical Immunology
• 出版年：2012
• 期刊代码：95_15216616
• 类别：imm
• 出版时间：March, 2012
• 卷：142
• 期：3
• 页码：237-242
• 文件大小：599 K

摘要

Cell signaling initiated by the B cell receptor is critical to normal development of B lymphocytes, most notably at the transitional B cell stage. Inhibition of this signaling pathway with the syk inhibitor, fostamatinib, has produced significant efficacy in lymphoid malignancies and autoimmune conditions. Here, we demonstrate that short-term use of fostamatinib impairs B lymphocyte development at the transitional stage without affecting mature B cell populations. Additionally, IL-10 producing B cells remained relatively constant throughout the treatment period. These findings provide insight into the mechanism of action of B cell receptor inhibition in autoimmune disease. As the development of agents targeting B cell receptor signaling proceeds, monitoring for long-term consequences as well as functional evaluation of B cell subsets may further improve our understanding of this rapidly growing class of novel agents.